A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human‐type receptors

Year: 2017

Type: article

Abstract: In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.

Source: EMBO Molecular Medicine

DOI: 10.15252/emmm.201707726

Authors: Robert P de Vries, Netanel Tzarum, Wenjie Peng, Andrew J Thompson, Iresha N Ambepitiya Wickramasinghe, Alba T Torrents de la Pena, Marielle J van Breemen, Kim M Bouwman, Xueyong Zhu, Ryan McBride, Wenli Yu, Rogier W Sanders, Monique H Verheije, Ian A Wilson, James C Paulson

Institutions: Scripps Research Institute, Utrecht University, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Cornell University, Weill Cornell Medicine

Language: English

Topic: Influenza Virus Research Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $7,990

Funders: U.S. Department of Energy, European Molecular Biology Organization, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Basic Energy Sciences, Biological and Environmental Research, H2020 European Research Council

OpenAlex ID: W2735426686